cefprozil 500 MG Oral Tablet
Generic Name: CEFPROZIL
Brand Name: CEFPROZIL
- Substance Name(s):
- CEFPROZIL
WARNINGS
BEFORE THERAPY WITH CEFPROZIL IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFPROZIL, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS.
IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-SENSITIVITY AMONG ß-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.
IF AN ALLERGIC REACTION TO CEFPROZIL OCCURS, DISCONTINUE THE DRUG.
SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefprozil, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.
difficile.
C.
difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin-producing strains of C.
difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.
difficile, and surgical evaluation should be instituted as clinically indicated.
DRUG INTERACTIONS
Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporin antibiotics.
Concomitant administration of probenecid doubled the AUC for cefprozil.
The bioavailability of the capsule formulation of cefprozil was not affected when administered 5 minutes following an antacid.
OVERDOSAGE
Single 5000 mg/kg oral doses of cefprozil caused no mortality or signs of toxicity in adult, weanling, or neonatal rats, or adult mice.
A single oral dose of 3000 mg/kg caused diarrhea and loss of appetite in cynomolgus monkeys, but no mortality.
Cefprozil is eliminated primarily by the kidneys.
In case of severe overdosage, especially in patients with compromised renal function, hemodialysis will aid in the removal of cefprozil from the body.
DESCRIPTION
Cefprozil is a semi-synthetic broad-spectrum cephalosporin antibiotic.
Cefprozil is a cis and trans isomeric mixture (≥90% cis).
The chemical name for the monohydrate is (6R,7R)-7-[(R)-2-amino-2-(p-hydroxyphenyl)acetamido]-8-oxo-3-propenyl-5-thia-1-azabicyclo [4.2.0]oct-2-ene-2- carboxylic acid monohydrate, and the structural formula is: Cefprozil is a white to yellowish powder with a molecular formula for the monohydrate of C18H19N3O5S.H2O and a molecular weight of 407.45.
Cefprozil tablets are intended for oral administration.
Cefprozil tablets contain cefprozil equivalent to 250 mg or 500 mg of anhydrous cefprozil.
In addition, each tablet contains the following inactive ingredients: magnesium stearate, methylcellulose, microcrystalline cellulose, sodium starch glycolate and titanium dioxide.
The 250 mg tablet also contains FD and C Yellow No.
6 Aluminum Lake.
structural formula
CLINICAL STUDIES
Study One: In a controlled clinical study of acute otitis media performed in the United States where significant rates of ßlactamase- producing organisms were found, cefprozil was compared to an oral antimicrobial agent that contained a specific ß-lactamase inhibitor.
In this study, using very strict evaluability criteria and microbiologic and clinical response criteria at the 10-16 days post-therapy follow-up, the following presumptive bacterial eradication/clinical cure outcomes (i.e., clinical success) and safety results were obtained: U.S.
Acute Otitis Media Study Cefprozil vs β-lactamase inhibitor-containing control drug EFFICACY: Pathogen % of Cases with Pathogen(n=155) Outcome S.
pneumoniae 48.4% cefprozil success rate 5% better than control H.
influenzae 35.5% cefprozil success rate 17% less than control M.
catarrhalis 13.5% cefprozil success rate 12% less than control S.
pyogenes 2.6% cefprozil equivalent to control Overall 100.0% cefprozil success rate 5% less than control SAFETY: The incidences of adverse events, primarily diarrhea and rash*, were clinically and statistically significantly higher in the control arm versus the cefprozil arm.
Age Group Cefprozil Control 6 months-2 years 21% 41% 3-12 years 10% 19% * The majority of these involved the diaper area in young children.
Study Two: In a controlled clinical study of acute otitis media performed in Europe, cefprozil was compared to an oral antimicrobial agent that contained a specific ß-lactamase inhibitor.
As expected in a European population, this study population had a lower incidence of ß-lactamase-producing organisms than usually seen in U.S.
trials.
In this study, using very strict evaluability criteria and microbiologic and clinical response criteria at the 10-16 days post-therapy follow-up, the following presumptive bacterial eradication/clinical cure outcomes (i.e., clinical success) were obtained: European Acute Otitis Media Study Cefprozil vs β-lactamase inhibitor-containing control drug EFFICACY: Pathogen % of Cases with Pathogen(n=47) Outcome S.
pneumoniae 51.0% cefprozil equivalent to control H.
influenzae 29.8% cefprozil equivalent to control M.
catarrhalis 6.4% cefprozil equivalent to control S.
pyogenes 12.8% cefprozil equivalent to control Overall 100.0% cefprozil equivalent to control SAFETY: The incidence of adverse events in the cefprozil arm was comparable to the incidence of adverse events in the control arm (agent that contained a specific ß-lactamase inhibitor).
HOW SUPPLIED
Cefprozil tablets USP, 250 mg and 500 mg are available as follows: Each white film-coated, oval tablet debossed with ‘LUPIN’ on one side and ‘500’ on the other side, contains the equivalent of 500 mg anhydrous cefprozil.
Bottles of 20 Tablets NDC 67296-0590-1 Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].
GERIATRIC USE
Geriatric Use: Of the more than 4500 adults treated with cefprozil in clinical studies, 14% were 65 years and older, while 5% were 75 years and older.
When geriatric patients received the usual recommended adult doses, their clinical efficacy and safety were comparable to clinical efficacy and safety in nongeriatric adult patients.
Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals to the effects of cefprozil cannot be excluded (see CLINICAL PHARMACOLOGY).
Cefprozil is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.
See DOSAGE AND ADMINISTRATION for dosing recommendations for patients with impaired renal function.
INDICATIONS AND USAGE
Cefprozil tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below: Upper Respiratory Tract: Pharyngitis/Tonsillitis: Caused by Streptococcus pyogenes.
NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route.
Cefprozil is generally effective in the eradication of Streptococcus pyogenes from the nasopharynx; however, substantial data establishing the efficacy of cefprozil in the subsequent prevention of rheumatic fever are not available at present.
Otitis Media: Caused by Streptococcus pneumoniae, Haemophilus influenzae (including ß-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including ß-lactamase-producing strains).
(See CLINICAL STUDIES.) NOTE: In the treatment of otitis media due to ß-lactamase producing organisms, cefprozil had bacteriologic eradication rates somewhat lower than those observed with a product containing a specific ß-lactamase inhibitor.
In considering the use of cefprozil, lower overall eradication rates should be balanced against the susceptibility patterns of the common microbes in a given geographic area and the increased potential for toxicity with products containing ß-lactamase inhibitors.
Acute Sinusitis: Caused by Streptococcus pneumoniae, Haemophilus influenzae (including ß-lactamase producing strains), and Moraxella (Branhamella) catarrhalis (including ß-lactamase-producing strains).
Lower Respiratory Tract: Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis: Caused by Streptococcus pneumoniae, Haemophilus influenzae (including ß-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including ß-lactamase-producing strains).
Skin and Skin Structure: Uncomplicated Skin and Skin-Structure Infections: Caused by Staphylococcus aureus (including penicillinase producing strains) and Streptococcus pyogenes.
Abscesses usually require surgical drainage.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefprozil tablets and other antibacterial drugs, cefprozil tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.
In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
PEDIATRIC USE
Pediatric Use: (See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.) The safety and effectiveness of cefprozil in the treatment of otitis media have been established in the age groups 6 months to 12 years.
Use of cefprozil for the treatment of otitis media is supported by evidence from adequate and well-controlled studies of cefprozil in pediatric patients.
(See CLINICAL STUDIES) The safety and effectiveness of cefprozil in the treatment of pharyngitis/tonsillitis or uncomplicated skin and skin-structure infections have been established in the age groups 2 to 12 years.
Use of cefprozil for the treatment of these infections is supported by evidence from adequate and well-controlled studies of cefprozil in pediatric patients.
The safety and effectiveness of cefprozil in the treatment of acute sinusitis have been established in the age groups 6 months to 12 years.
Use of cefprozil in these age groups is supported by evidence from adequate and well-controlled studies of cefprozil in adults.
Safety and effectiveness in pediatric patients below the age of 6 months have not been established for the treatment of otitis media or acute sinusitis, or below the age of 2 years for the treatment of pharyngitis/tonsillitis or uncomplicated skin and skin-structure infections.
However, accumulation of other cephalosporin antibiotics in newborn infants (resulting from prolonged drug half-life in this age group) has been reported.
PREGNANCY
Pregnancy: Teratogenic Effects- Pregnancy Category B: Reproduction studies have been performed in rabbits, mice, and rats using oral doses of cefprozil of 0.8, 8.5, and 18.5 times the maximum daily human dose (1000 mg) based upon mg/m2, and have revealed no harm to the fetus.
There are, however, no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
NUSRING MOTHERS
Nursing Mothers: Small amounts of cefprozil (less than 0.3% of dose) have been detected in human milk following administration of a single 1 gram dose to lactating women.
The average levels over 24 hours ranged from 0.25 to 3.3 mcg/mL.
Caution should be exercised when cefprozil tablets are administered to a nursing woman, since the effect of cefprozil on nursing infants is unknown.
INFORMATION FOR PATIENTS
Information for Patients: Patients should be counseled that antibacterial drugs including cefprozil should only be used to treat bacterial infections.
They do not treat viral infections (e.g., the common cold).
When cefprozil are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.
Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefprozil or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued.
Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic.
If this occurs, patients should contact their physician as soon as possible.
DOSAGE AND ADMINISTRATION
Cefprozil tablets are administered orally.
Population/Infection Dosage (mg) Duration (days) ADULTS (13 years and older) UPPER RESPIRATORY TRACT Pharyngitis/Tonsillitis 500 q24h 10 a Acute Sinusitis 250 q12h or 10 (For moderate to severe infections, the higher dose should be used) 500 q12h LOWER RESPIRATORY TRACT Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis 500 q12h 10 SKIN AND SKIN STRUCTURE Uncomplicated Skin and Skin Structure Infections 250 q12h or 10 500 q24h or 500 q12h CHILDREN (2 years-12 years) UPPER RESPIRATORY TRACT b Pharyngitis/Tonsillitis 7.5 mg/kg q12h 10 a SKIN AND SKIN STRUCTURE b Uncomplicated Skin and Skin Structure Infections 20 mg/kg q24h 10 INFANTS and CHILDREN (6 months-12 years) UPPER RESPIRATORY TRACT b Otitis Media 15 mg/kg q12h 10 (See INDICATIONS AND USAGE and CLINICAL STUDIES ) Acute Sinusitis 7.5 mg/kg q12h or 10 (For moderate to severe infections, the higher dose should be used) 15 mg/kg q12h a In the treatment of infections due to Streptococcus pyogenes, cefprozil for oral suspension should be administered for at least 10 days.
b Not to exceed recommended adult doses.
Renal Impairment: Cefprozil may be administered to patients with impaired renal function.
The following dosage schedule should be used.
Creatinine Clearance (mL/min) Dosage (mg) Dosing Interval 30-120 standard standard 0-29* 50% of standard standard *Cefprozil is in part removed by hemodialysis; therefore, cefprozil should be administered after the completion of hemodialysis.
Hepatic Impairment: No dosage adjustment is necessary for patients with impaired hepatic function.